Free fatty acids inhibit adrenocorticotropin and cortisol secretion stimulated by physical exercise in normal men

SummaryBackground  The basal circulating levels of ACTH and cortisol, but not the ACTH/cortisol response to hCRH, are significantly reduced by free fatty acid (FFA) infusion.Objective  To verify whether FFA infusion modifies the ACTH/cortisol response to physical exercise, a well‐known activator of the HPA axis at suprapituitary level.Design  Exercise tests on a bicycle ergometer during infusion of a lipid‐heparin emulsion (LHE) (experimental test) or normal saline (NaCl 0·9%) (control test).Setting  Department of Cardiology at the University‐Hospital.Subjects  Seven healthy male subjects aged 25–33 years.Interventions  On two mornings, at weekly intervals, LHE or saline were infused for 60 min; infusion started 10 min before exercise test on a bicycle ergometer, which lasted about 15 min.Main outcome measures  Circulating ACTH/cortisol levels and physiological variables during physical exercise.Results  FFA levels (0·4 ± 0·1 mEq/l) remained constant during control test, whereas they progressively rose (peak at 60 min, 2·7 ± 1·0 mEq/l) during LHE infusion. Neither basal nor exercise‐induced changes in physiological variables were modified by LHE infusion. Both ACTH and cortisol increased during exercise, with peak levels at 20 min and 30 min (control test: 103% and 42%, P < 0·001; experimental test: 28·5% and 18·6%, P < 0·05 higher than baseline, respectively).Both ACTH and cortisol responses were significantly lower in the experimental than in the control test (at 20 min P < 0·002 and at 30 min P < 0·05 for ACTH; at 20 min P < 0·05 and at 30 min, 40 min and 50 min P < 0·001 for cortisol).Conclusions  These data represent the first demonstration of an inhibitory action of increased circulating FFA levels on the HPA axis under stimulatory conditions (i.e. physical exercise, a challenge acting at suprapituitary level). In contrast, previous studies did not show FFA effects on the CRH‐induced ACTH/cortisol response. Therefore, our data suggest negative effects of FFAs on the HPA axis at hypothalamic or higher centres in the central nervous system.